sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death英文论文.pdf

Sumoylation of Hypoxia-Inducible Factor-1a Ameliorates Failure of Brain Stem Cardiovascular Regulation in Experimental Brain Death 1,2 2 2 2 2 2 Julie Y. H. Chan , Ching-Yi Tsai , Carol H. Y. Wu , Faith C. H. Li , Kuang-Yu Dai , Enya Y. H. Sun , 2 2 Samuel H. H. Chan *, Alice Y. W. Chang * 1 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China, 2 Center for Translational Research in Biomedical Sciences, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China Abstract Background: One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM). RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1a (HIF-1a) plays a pro-life role in experimental brain death, and HIF-1a is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1a in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death. Methodology/Principal Findings: A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect